Adverse Effects of Fluoroquinolones - Risk Factors and Interactions

Risk Factors and Interactions

Certain patient groups are at increased risk of fluoroquinolone ADRs. A 1998 retrospective survey of the use of the fluoroquinolones in the pediatric population showed that the fluoroquinolones were oftentimes prescribed in children, (although their use is not approved in this age group), and that numerous serious side effects had been recorded. Fluoroquinolones are not recommended in patient groups that are predisposed to adverse events (for example, because of diabetes, G6PD deficiency, renal impairment, myasthenia gravis, previous psychiatric, seizure disorder, or children (under 18)). An alternative antibiotic class should be used wherever possible in such patients, and,if used, special caution is advised; for example, possible dosage reduction may be required as well as extra vigilance for adverse reactions. There is also an increased risk of adverse events in the elderly, including tendon ruptures and seizures. Use in children or pregnant or breast-feeding women is not recommended and should be avoided. In the UK, the prescribing indications for fluoroquinolones for children is severely restricted. Only inhalant anthrax and pseudomonal infections in cystic fibrosis infections are licensed indications in the UK due to ongoing safety concerns. At the first sign of psychiatric, neurological, peripheral neuropathy, tendonitis, or hypersensitivity reactions, fluoroquinolones should be discontinued. Quinolones are contraindicated in patients having had previous quinolone-related tendinopathy. Dose, length of time, and number of exposures to fluoroquinolones, as well as combination with corticosteroids, NSAIDs, or theophylline, increase the risk adverse reactions. Concurrent use of corticosteroids increases the risk of multiskeletal injury, manifesting as chronic tendonitis or spontaneous ruptures of tendons, muscles, and cartilage. Concurrent use of NSAIDs may induce severe and prolonged seizures including status epilepticus. Most cases of fluoroquinolone-precipitated seizures occur in the elderly or those with severe cerebral arteriosclerosis, epilepsy, brain tumour, anoxia, and alcohol dependence, as well as those taking theophylline or the NSAIDs. Those who are benzodiazepine-dependent or in benzodiazepine withdrawal have a higher rate of adverse severe CNS effects possibly due to fluoroquinolones' displacement of benzodiazepines from their receptor site or pre-existing GABA underactivity due to withdrawal, thus leading to an increased sensitivity to fluoroquinolone toxicity. Articaine may worsen certain symptoms in an individual with fluoroquinolone toxicity. There have been persistent reports of unexplained paresthesia following the use of articaine (burning, tingling, and sometimes sharp shooting pains in tissues previously anesthetized with this anesthetic) during dental procedures involving patients having had adverse reactions to the fluoroquinolones. Broad spectrum antibacterials including cephalosporins, Fluoroquinolones (and clindamycin) have been associated with Clostridium difficile, a potentially life-threatening super-infection. Use of quinolones is also highly associated with colonisation with MRSA compared to some other antibiotic classes. Shigella toxin expression in EHEC infections has been shown to be upregulated following fluoroquinolone administration. Fluoroquinolones can have serious and potential fatal reaction when taken with certain other drugs. Some agents decrease theophylline clearance and thus increase toxicity. Warfarin is affected by many many drugs including fluoroquinolones and frequency of INR monitoring needs to be increased in those prescribed both agents.